| First Author | Negishi K | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 8844 |
| PubMed ID | 35614093 | Mgi Jnum | J:344092 |
| Mgi Id | MGI:7283606 | Doi | 10.1038/s41598-022-12418-8 |
| Citation | Negishi K, et al. (2022) An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility. Sci Rep 12(1):8844 |
| abstractText | Pathogenic variants in myosin heavy chain (Myh11) cause familial thoracic aortic aneurysms and dissections (FTAAD). However, the underlying pathological mechanisms remain unclear because of a lack of animal models. In this study, we established a mouse model with Myh11 K1256del, the pathogenic variant we found previously in two FTAAD families. The Myh11(K/K) aorta showed increased wall thickness and ultrastructural abnormalities, including weakened cell adhesion. Notably, the Myh11(K/+) mice developed aortic dissections and intramural haematomas when stimulated with angiotensin II. Mechanistically, integrin subunit alpha2 (Itga2) was downregulated in the Myh11(K/K) aortas, and the smooth muscle cell lineage cells that differentiated from Myh11(K/K) induced pluripotent stem cells. The contractility of the Myh11(K/K) aortas in response to phenylephrine was also reduced. These results imply that the suboptimal cell adhesion indicated by Itga2 downregulation causes a defect in the contraction of the aorta. Consequently, the defective contraction may increase the haemodynamic stress underlying the aortic dissections. |
